We propose to investigate the impact of blast-related TBI in returning OIF/OEF combat veterans using FDG-PET and diffusion tensor imaging (DTI). The primary objective will be to characterize white matter integrity using DTI, as well as conduct Brodmann analyses and measure glucose metabolic activity using FDG-PET in combat veterans exposed to blast wave with and without a diagnosis of TBI. We will also acquire anatomic MRI for volumetric analysis. The secondary objective will be to examine the relationship between white matter integrity and functional imaging findings to neuropsychological function and to activities of daily living (Functional Assessment Questionnaire and Quality of Living questionnaire). We will also examine in this cohort the effect of PTSD on the imaging and cognitive outcomes. We will recruit a cohort of 16 OEF and OIF combat veterans per year for three years who have sustained mild TBI following blast injury and a group of 16 age, education, and sex matched OIF/OEF veteran controls per year for three years who do not have a diagnosis of mild TBI from blast exposure. This study will help identify for the first time neuropsychological and neural correlates of mild TBI as a result of exposure to blast wave. The use of various types of imaging modalities proposed here will add previously unknown, critically important identification and validation to the diagnosis of TBI and its cognitive consequences in combat veterans exposed to blast. With the growing number of improvised explosive device casualties and resulting TBI diagnoses in OIF/OEF veterans, the full impact of acute and repeated blast exposure on individual performance and long-term health is unknown. Indeed, many OIF/OEF veterans currently presenting to VA hospitals with symptoms consistent with mild TBI were never recognized prior to discharge from the armed forces. While the extent of the problem is not known, it is without doubt substantial and there is a growing concern that blast may produce long-term injury to military personnel. Traumatic brain injury will become an increasingly costly health issue for the US with regard to the escalating cost for federal programs addressing medical treatment and intervention, given the high frequency of blast exposure in returning OIF/OEF veterans. Understanding the neural, cognitive and functional sequelae in these veterans will enable the earliest possible intervention strategies, when treatment may be most effective. Intervention may help to alleviate not only the cognitive problems associated with mild TBI but the functional difficulties (job-related problems, relationship problems) that will certainly reduce costs, but importantly, will prolong quality of life in these veterans. PUBLIC HEALTH RELEVANCE: Little work has been done in veterans on the problem of blast-related TBI, particularly mild TBI, and its association with cognitive decline. Elucidating the neurobiological and neuropsychological aspects, as well as the functional difficulties that arise in many returning veterans as a result of blast-exposure TBI is essential in determining appropriate treatment and long-term care of returning veterans from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) who have sustained head injury during their tours of duty. This study will help identify for the first time neuropsychological and neural correlates of mild TBI as a result of exposure to blast wave. With the growing number of improvised explosive device casualties and resulting mild TBI diagnoses in OIF/OEF veterans, the full impact of acute and repeated blast exposure on individual performance and long-term health is unknown. Indeed, many OIF/OEF veterans currently presenting to VA hospitals with symptoms consistent with mild TBI were never recognized prior to discharge from the armed forces. These cases are only now being recognized as related to single or often multiple blast exposures. While the extent of the problem is not known, it is without doubt substantial and there is a growing concern that blast may produce long-term injury to military personnel. TBI will become an increasingly costly health issue for the US with regard to the escalating cost for federal programs addressing medical treatment and intervention, given the high frequency of head injury in returning OIF/OEF veterans. Understanding the neural, cognitive and functional sequelae in these veterans will enable the earliest possible intervention strategies, when treatment may be most effective to alleviate not only the cognitive sequelae associated with mild TBI but the functional difficulties (job-related problems, relationship problems) that often arise in returning veterans. Delineating the cognitive and neurobiological profile of blast-related TBI in returning OIF/OEF veterans will provide the scientific field with important information with regard to the development of adequate preparation, intervention, treatment, and practical planning. Furthermore, the findings from this study may advance scientific knowledge with regard to the underlying neurobiological underpinnings of the complex interaction of blast-related mild TBI and concomitant cognitive and functional deficits. Intervention and prevention strategies at the earliest possible stage aimed at prolonging well-being, will certainly reduce costs, but importantly, will prolong quality of life in these veterans.